This project will involve two general areas of investigation into the course and treatment of myocardial ichemia. The first area involves those early changes occurring in an ischemic event that may result in further cardiac damage, chronic myocardial impairment, or cell death: 1) Coupling of Glycogen and Phosphorylase to Sarcoplasmic Reticulum - The mechanism of phosphorylase depletion in myocardial stress or ischemia. We will develop an immunoassay for cardiac phosphorylase. 2) Effect of palmitylcarnitine on membrane ATPases and transport - Palmitylcarnitine levels will be measured at various times of ischemia to correlate with the assay kinetic results. 3) Binding of Clq to ischemic myocardium occurs within minutes after the onset of myocardial ischemia prior to increases in vascular permeability. 4) Ultrastructure Studies - Studies on the early changes in the myocardial ultrastructure in ischemia. In the past year, the development of freeze-fracture and freeze-drying techniques have been added. 5) Mitochdrial Lipid Metabolism - A project to study the mechanism of ischemic induced increases in fatty acyl intermediates and their effect on mitochondrial substrate utilization. The second are a studies problems involved in intervention in myocardial ischemia. The first involves techniques to improve cardiac preservation during ischemic arrest and cardiopulmonary bypass and the second involves the changes in saphenous vein grafts after aorto-coronary bypass. The saphenous vein is highly reactive to catecholamine induced vasoconstriction which is in marked contrast to native coronary vessels. We will examine changes in pharmacologic response and smooth muscle contractility compared to in situ saphenous veins. The pattern of reinnervation will also be studied.